Objective: To describe the phenotypic features of an ethnically homogenous group of patients with Fanconi-Bickel syndrome harboring the p.R310X mutation.
Methods: The study group consisted of eight patients from a single Bedouin family with clinically and molecularly diagnosed Fanconi-Bickel syndrome who had been followed at the same tertiary medical center for 8 years or more. All were homozygous for the p.R310X mutation. The medical files were reviewed for presenting signs and symptoms, laboratory and imaging findings, treatment regimens, and disease severity over time.
Results: Seven patients were diagnosed at our center before age 1 year, and one transferred from another center at age 16 years. Most patients presented with failure to thrive and/or hepatomegaly. All had short stature and doll-like facies. Most had biochemical abnormalities. Evaluation of the long-term findings revealed a wide spectrum of disease severity according to the following parameters: growth patterns, maximal electrolyte replacement therapy, skeletal and renal complications, frequency of follow-up visits, and hospitalizations for disease exacerbations. There was no apparent association of the clinical picture at presentation and later disease severity.
Conclusion: Fanconi-Bickel syndrome has a broad phenotypic variability in patients harboring the same homozygous p.R301X mutation. This finding might be explained by genetic elements such as modifier genes and epigenetic factors, as well as the effects of still-undetermined environmental and nutritional factors.